The past few years have witnessed an extraordinary number of important developments in the study of compensatory and maladaptive responses to cardiac dysfunction. It now seems clear that the process whereby the heart remodels in response to left ventricular injury is of paramount importance in the expression of clinical heart failure. There have been parallel attempts by basic scientists and clinical investigators to understand better the fundamental biologic processes that underlie remodeling and to assess numerous new treatments--especially angiotensin-converting enzyme inhibitors. A general consensus seems to be emerging that holds that the response of the heart to acute injury includes a number of highly compensatory and adaptive mechanisms that ultimately become maladaptive and contribute to cardiomegaly and severe congestive heart failure. Such mechanisms undoubtedly include local and systemic release of cytokines, peptides, and neurohormones, and altered loading conditions leading to unusual mechanical forces on cardiac myocytes and other cells of the heart. At the organ level there is hypertrophy, dilatation and growth of the interstitium. Preliminary evidence also suggests there may be some "remodeling" at the cardiac myocyte level. Reduction in peripheral vasodilator reserve is seen in experimental animal models of heart failure. Patients with heart failure also develop an endothelial-dependent form of peripheral vascular dysfunction expressed clinically as an attenuated ability to dilate in response to such stimuli as acetylcholine. The transition point whereby these myocardial and peripheral vascular abnormalities become clearly dysfunctional and contribute toward the full clinical expression of heart failure remains to be further investigated.